Ars2 promotes proper replication-dependent histone mRNA 3' end formation.

Ars2 promotes proper replication-dependent histone mRNA 3' end formation.
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DOI:
10.1016/j.molcel.2011.12.020
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发表时间:
2012-01-13
期刊:
影响因子:
16
通讯作者:
Thompson, Craig B.
Thompson, Craig B.
中科院分区:
生物学1区
文献类型:
--
作者:
Gruber, Joshua J.;Olejniczak, Scott H.;Yong, Jeongsik;La Rocca, Gaspare;Dreyfuss, Gideon;Thompson, Craig B.

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Ars2是核帽结合复合物的一个组成部分,有助于microRNA的生物合成,是细胞增殖所必需的。在这里,我们扩展了Ars2依赖的microRNA的库,并确定Ars2调节许多mRNA,其中最大的定义子集编码组蛋白。组蛋白mRNA在哺乳动物mRNA中是独特的,因为它们通常不被多聚腺苷酸化,而是沿着3 '茎环切割。在Ars2耗竭后,观察到正确加工的组蛋白mRNA显著减少,同时多聚腺苷酸化组蛋白转录物增加。此外,Ars2与组蛋白mRNA和非编码RNA 7SK物理相关。敲低7SK导致切割的多聚腺苷酸化组蛋白转录物的比率增强,这种效应依赖于Ars2。总之,数据表明Ars2有助于组蛋白mRNA 3′端的形成和表达,Ars2的这些功能特性通过与7SK RNA的相互作用而受到负调控。
Ars2 is a component of the nuclear cap-binding complex that contributes to microRNA biogenesis and is required for cellular proliferation. Here we expand on the repertoire of Ars2-dependent microRNAs and determine that Ars2 regulates a number of mRNAs, the largest defined subset of which code for histones. Histone mRNAs are unique among mammalian mRNAs because they are not normally polyadenylated, but rather cleaved following a 3′ stem loop. A significant reduction in correctly processed histone mRNAs was observed following Ars2 depletion, concurrent with an increase in polyadenylated histone transcripts. Furthermore, Ars2 physically associated with histone mRNAs and the non-coding RNA 7SK. Knockdown of 7SK led to an enhanced ratio of cleaved to polyadenylated histone transcripts, an effect dependent on Ars2. Together, the data demonstrate that Ars2 contributes to histone mRNA 3′ end formation and expression and these functional properties of Ars2 are negatively regulated by interaction with 7SK RNA.
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